(S)-[(2R,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol → 3-Methyl-4-phenyl-2-(2,2,2-trifluoroacetamido)-(2S,3R)-pent-4-enoic Acid

Participants

Reaction Conditions

Reaction Steps

To a solution of hexamethyldisilazane (6.19 g, 8.0 mL, 38.5 mmol) in THF (20 mL at −20° C. under N2) was added BuLi (1.6 M solution in hexane, 20 mL, 32 mmol). The solution was stirred at −20° C. for 20 min and added via cannula to a suspension of 13 (2.00 g, 6.64 mmol), quinidine (4.30 g, 13.27 mmol), and aluminum isopropoxide (2.04 g, 10.0 mmol) in THF (70 mL) at −78° C. The solution was allowed to come to ambient temperature, and stirring was continued for 18 h. The mixture was next diluted with EtOAc (250 mL) and washed with 1 N HCl (3×75 mL). The combined washings were extracted with EtOAc (50 mL). The organic solutions were combined and extracted with 6% NaHCO3 (7×50 mL). The aqueous extracts were combined, cooled in an ice bath, acidified (pH 1) with 6 N HCl, and extracted with EtOAc (4×50 mL). The organic extracts were combined, washed with 5 M NaCl (20 mL), dried, and evaporated to give 1.54 g (77%) of 14 as a pale yellow semi-solid: Rf 0.76 (95:5:1 DCM-CH3OH—HOAc); 1H NMR δ 9.10 (1H, br), 7.33 (5H, m), 6.42 (1H, d, J=8.2 Hz), 5.37 (1H, m), 5.15 (1H, s), 4.68 (1H, dd, J=8.6 and 3.4 Hz), 3.57 (1H, m), 1.31 (3H, d, J=7.2 Hz); 13C NMR δ 174.8, 156.6 (m), 148.6, 140.8, 128.6, 128.2, 126.7, 115.1, 55.0, 39.5, 14.0; MS APCI+ m/z 302.1010 [M+H]+, (calcd for C14H15F3NO3, 302.1004).

Provenance & Evidence